The liver plays various roles in a body, such as lipid metabolism, detoxication, excretion of bile, storage of various nutrients, hematopoiesis or blood coagulation, and the control of a volume of circulating blood, and is one of the essential organs for supporting life. More specifically, first, the liver has a function of managing energy metabolism, so that all nutrients absorbed from food can be metabolized into substances capable of producing energy in the liver, and thus are provided to or stored in the entire body. Second, the liver has the function of synthesizing, storing and distributing approximately 2,000 enzymes, albumin, serum proteins of coagulation factors, bile acid, or lipids such as phospholipids and cholesterol. Third, as detoxication and degradation functions, the liver can detoxicate a drug, alcohol, or a toxic substance, excrete a variety of metabolites and have an immune function, which provides a critical role in life support.
Hepatitis, which represents inflammation in the liver, accounts for most of the liver diseases, and may be divided into acute hepatitis and chronic hepatitis according to modality, and may be divided into viral hepatitis, alcoholic hepatitis and drug-induced hepatitis according to cause. In addition, liver diseases caused by such abnormalities include fatty liver, hepatitis, liver cirrhosis and liver cancer. The pathogenesis of a liver disease has not been completely discovered, but it is known that fatty liver is primarily generated and then followed by secondary cell damage, and then a progressive liver disease such as steatohepatitis or liver cirrhosis is developed. In addition, since the liver disease is not found until it has progressed considerably due to no subjective symptom at an early stage, it is the leading cause of death not only in Korea but also in the world.
Currently, treatments for a liver disease, which have been generally used, are broadly divided into a dietary therapy and a drug therapy, and in most cases, these two methods are used together. The drug therapy against a liver disease may use drugs having various action mechanisms according to the cause and type of a liver disease, and examples of the drugs may generally be drugs, for example, hepatocyte regeneration promoters and liver-function supplements, such as ursodexoycholic acid, silymarine, biphenyldimethyldicarboxylate (DDB), glutathione, carnitine orotate, glycyrrhizin and multiple vitamins; antiviral agents such as acyclovir; immunosuppressants such as corticosteroid, 6-mercaptopurine (6-MP) and azathioprine; and fibrosis inhibitors such as D-penicillamine. However, due to limited hepatic protection and side effects of these agents, there is difficulty in using these drugs for fundamental treatment of a liver disease. Therefore, today, while there is a growing interest in natural substance-derived therapeutic agents for a liver disease, which have excellent biocompatibility with little concern about side effects, and such therapeutic agents become the subject of a major project (Korean Patent Application Publication No. 10-2015-0098161). However, in the case of most natural substances, little basic research on an effective dose and an exact pharmacological effect was investigated, and thus the use thereof as a therapeutic agent for a liver disease is difficult.
Meanwhile, Moutan Cortex Radicis, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), has been widely used to eliminate heat from the blood and blood stasis by promoting active blood circulation, and treat ischemia in oriental medicine. A Moutan Cortex Radicis extract has been reported to inhibit the release of IL-8 and MCP-1, which are chemokines, in vitro, and the expression of iNOS and COX-2, which are inflammatory mediators. The Moutan Cortex Radicis extract has been known to have a very high inhibitory activity against HIV integrase, and it has been known that paeonol, a main component of Moutan Cortex Radicis, inhibits xanthine oxidase to inhibit the generation of reactive oxygen species, and inhibits the release of an inflammatory mediator, TNF-α.
Against this backdrop, the inventors made an effort to find a natural substance as an agent for preventing or treating a liver disease, and when a fraction of the Moutan Cortex Radicis extract was treated to cure various types of liver injury including impaired blood flow caused by hepatic ischemia and reperfusion, acute hepatic failure caused by galactosamine/lipopolysaccharide (GalN/LPS) and drug-mediated liver injury caused by acetaminophen (APAP), the fraction has an excellent liver protective effect, and therefore the present invention was completed.